Methylation differences between assisted reproductive technology-conceived and naturally conceived children near BRCA1 and NBR2

Recent studies have shown that newborns conceived using assisted reproductive technology (ART) exhibited significantly different DNA methylation (DNAm) profiles at birth compared to those conceived naturally. Of note was the observation of increased DNAm at the promoter region of BRCA1/NBR2 in ART-conceived newborns. However, it remains unclear if these DNAm differences persist after birth. Using the Norwegian Mother, Father, and Child Cohort Study (MoBa), a large-scale population-based pregnancy cohort with extensive longitudinal data collected through biological samples and questionnaires, we generated longitudinal DNAm data for 105 ART-conceived and 250 naturally conceived children at birth and at ages 3–22 years. DNAm differences in the BRCA1/NBR2 promoter between ART- and naturally conceived children, at birth and postnatally, were tested using linear mixed model with adjustment for maternal and newborn covariates. While ART-conceived children showed subtle hypermethylation at birth and postnatally, the differences diminished over time and did not remain statistically significant after multiple testing correction. Our findings suggest that subtle hypermethylation at the BRCA1/NBR2 promoter in ART-conceived children may represent an ART-associated epigenetic signature, although further studies in larger populations are needed to clarify its persistence and significance.